The link between early childhood lower airway symptoms, airway hyperresponsiveness, and school-age lung function.

BACKGROUND: The role of early airway hyperresponsiveness (AHR) in the lung function of school-age children is currently unclear. OBJECTIVE: To conduct a prospective follow-up study of lung function in schoolchildren with a history of lower airway symptoms and AHR to methacholine in early childhood and to compare the findings to schoolchildren with no previous or current lung diseases. We also explored symptoms and markers of type 2 inflammation. METHODS: In 2004 to 2011, data on atopic markers, lung function, and AHR to methacholine were obtained from 193 symptomatic children under 3 years old. In 2016 to 2018, a follow-up sample of 84 children (median age, 11 years; IQR, 11-12) underwent measurements of atopic parameters, lung function, and AHR to methacholine. Moreover, in 2017 to 2018, 40 controls (median age, 11 years; IQR, 9-12) participated in the study. RESULTS: Schoolchildren with early childhood lower airway symptoms and increased AHR had more frequent blood eosinophilia than their peers without increased AHR and lower prebronchodilator forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity Z-scores than those without increased AHR and controls. Post-bronchodilator values were not significantly different between the two AHR groups. Atopy in early childhood (defined as atopic eczema and at least 1 positive skin prick test result) was associated with subsequent lung function and atopic markers, but not AHR. CONCLUSION: In symptomatic young children, increased AHR was associated with subsequent obstructive lung function, which appeared reversible by bronchodilation, and blood eosinophilia, indicative of type 2 inflammation.

The Finnish versions of food allergy quality of life questionnaires including parent form 10.

AIM: Examining health-related quality of life (HRQoL) is important to improve patient care. In this study, we translate and evaluate the Finnish versions of the Food Allergy Specific Quality of Life Questionnaires (FAQLQs) from a Finnish perspective and undertake a detailed evaluation of the 10-question Parent Form Questionnaire (FAQLQ-PF10). METHODS: This validation study was performed to evaluate the Finnish versions of the FAQLQs. Validation was performed by analysing clinical characteristics, factor loadings and Cronbach's α reliability estimates. The inclusion criteria for participants in this study were having a doctor-diagnosed food allergy or being a parent of a child with a doctor-diagnosed food allergy and being able to answer the questionnaire in Finnish. RESULTS: Altogether, 247 questionnaires were completed in this study. Most of the respondents had multiple food allergies (77%, 189/247). Spearman's correlations related to the 10-question parent form (FAQLQ-PF10), the 30-question parent form (FAQLQ-PF) and the Food Allergy Severity Measurement-Parent Form (FAIM-PF) were statistically significant (p value = 0.000-0.007). The reliability of the Finnish versions of the FAQLQs measured by Cronbach's α was overall good (0.75-0.981). CONCLUSION: The Finnish versions of the FAQLQs are reliable and suitable to use, and the FAQLQ-PF10 has good usability.

Long-term changes in milk component immunoglobulins reflect milk oral immunotherapy outcomes in Finnish children.

BACKGROUND: Milk oral immunotherapy (OIT) may increase the amount of milk protein that can be ingested without triggering an allergic reaction. It is important to understand why some patients benefit from the treatment while others do not. OBJECTIVE: The aim was to define the differences in the milk allergen component-specific (casein, α-lactalbumin, ß-lactoglobulin) immunoglobulin (sIg [sIgE, sIgG4, and sIgA]) levels relative to the long-term outcomes of milk OIT. METHODS: In this long-term, open-label follow-up study, 286 children started milk OIT between 2005 and 2015. Follow-up data were collected at two points: the post-buildup phase and long term (range 1-11 years, median 6 years). Comparisons of sIg levels were made among three outcome groups of self-reported long-term milk consumption (high-milk dose, low-milk dose, and avoidance). RESULTS: A total of 168 (59%) of the 286 patients on OIT participated. Most patients (57%) were in the high-dose group; here, 80% of these patients had a baseline casein sIgE value less than 28 kUA/L, they had the lowest casein sIgE levels at all time (p < .001), their casein sIgG4/IgE levels increased, and long-term casein sIgA was highest compared with the low-dose and avoidance groups (p = .02). Low-milk dose group had the highest casein sIgG4/IgE levels in long term (p = .002). CONCLUSION: The baseline Ig profiles and responses to milk OIT differed depending on long-term milk consumption. Lower casein sIgE levels were associated with better outcome. Milk casein sIgA differed in the long term among high-milk consumers.

Topical tacrolimus versus corticosteroids in childhood moderate-to-severe atopic dermatitis and the impact on airway inflammation: a long-term randomized open-label study.

BACKGROUND: Childhood atopic dermatitis (AD) is often followed by other atopic comorbidities such as asthma. AIM: To compare the effectiveness of topical tacrolimus (TAC) and topical corticosteroids (TCSs) and their impact on airway inflammation and bronchial hyperresponsiveness in patients with paediatric AD. METHODS: This was a 3-year randomized open-label comparative follow-up study of 152 1-3-year-old children with moderate-to-severe AD (trial registration: EudraCT2012-002412-95). Frequent study visits including clinical examinations, laboratory investigations (total IgE, specific IgEs, blood eosinophils), skin prick and respiratory function tests to assess airway inflammation and bronchial hyperresponsiveness (exhaled nitric oxide, airway responsiveness to exercise and methacholine) were performed. RESULTS: Changes in eczema parameters at 36 months were similar in the TCS and TAC groups for mean body surface area (BSA) difference 1.4 [95% confidence interval (CI) -1.48 to 4.19); P = 0.12], mean Eczema Area and Severity Index (EASI) difference 0.2 (95% CI -1.38 to 1.82; P = 0.2), mean Investigator's Global Assessment (IGA) difference, 0.3 (95% CI -0.12 to 0.67; P = 0.12) and mean transepidermal water loss (TEWL) difference at the eczema site, -0.3 (95% CI -4.93 to 4.30; P = 0.96) and at the control site, 1.4 (95% CI -0.96 to 3.60, P = 0.19). The control-site TEWL increased more towards the end of follow-up in the TCS vs. TAC group (mean change difference -4.2, 95% CI -8.14 to -0.29; P = 0.04). No significant impact on development of airway inflammation or bronchial hyperresponsiveness occurred in early effective eczema-treatment responders vs. others ('early' vs. 'other' response was defined as the difference in treatment response to airway outcomes in BSA, EASI or IGA at 3 months). CONCLUSION: Children with moderate-to-severe AD benefit from long-term treatment with TCS or TAC. There were no significant differences in treatment efficacy. No differences in the impact on airways occurred between early effective treatment responders vs. others.

Overweight and exercise-induced bronchoconstriction - Is there a link?

BACKGROUND: The objective of this study was to evaluate the role of body mass index with regard to exercise performance, exercise-induced bronchoconstriction (EIB), and respiratory symptoms in 7- to 16-year-old children. METHODS: A total of 1120 outdoor running exercise challenge test results of 7- to 16-year-old children were retrospectively reviewed. Lung function was evaluated with spirometry, and exercise performance was assessed by calculating distance per 6 minutes from the running time and distance. Respiratory symptoms in the exercise challenge test were recorded, and body mass index modified for children (ISO-BMI) was calculated for each child from height, weight, age, and gender according to the national growth references. RESULTS: Greater ISO-BMI and overweight were associated with poorer exercise performance (P < .001). In addition, greater ISO-BMI was independently associated with cough (P = .002) and shortness of breath (P = .012) in the exercise challenge. However, there was no association between ISO-BMI and EIB or with wheeze during the exercise challenge. CONCLUSION: Greater ISO-BMI may have a role in poorer exercise performance and appearance of respiratory symptoms during exercise, but not in EIB in 7- to 16-year-old children.

Impulse oscillometry and free-running tests for diagnosing asthma and monitoring lung function in young children.

BACKGROUND: Separating individuals with viral-induced wheezing from those with asthma is challenging, and there are no guidelines for children under 6 years of age. Impulse oscillometry, however, is feasible in 4-year-old children. OBJECTIVE: To explore the use of impulse oscillometry in diagnosing and monitoring asthma in young children and evaluating treatment response to inhaled corticosteroid (ICS). METHODS: A total of 42 children (median age 5.3 years, range 4.0-7.9 years) with physician-diagnosed asthma and lability in oscillometry were followed for 6 months after initiation of ICS treatment. All children performed the 6-minute free-running test and impulse oscillometry at 3 time points. After the baseline, they attended a second visit when they had achieved good asthma control and a third visit approximately 60 days after the second visit. A positive ICS response was defined as having greater than 19 points in asthma control test and no hyperreactivity on the third visit. RESULTS: In total, 38 of 42 children responded to ICS treatment. Exercise-induced increases of resistance at 5 Hz decreased after ICS treatment (61% vs 18% vs 13.5%, P < .001), and running distance during the 6-minute test was lengthened (800 m vs 850 m vs 850 m, P = .001). Significant improvements in childhood asthma control scores occurred between the baseline and subsequent visits (21 vs 24 vs 24, P < .001) and acute physicians' visits for respiratory symptoms (1, (0-6) vs 0, (0-2), P = .001). Similar profiles were observed in children without aeroallergen sensitization and among those under 5 years of age. CONCLUSION: Impulse oscillometry is a useful tool in diagnosing asthma and monitoring lung function in young children.

Airway hyperresponsiveness, remodeling and inflammation in infants with wheeze.

BACKGROUND: The relationship of airway hyperresponsiveness to airway remodeling and inflammation in infants with wheeze is unclear. OBJECTIVE: To investigate airway hyperresponsiveness, remodeling and inflammation in infants with wheeze and troublesome breathing. METHODS: Inclusion criteria were as follows: full-term, 3-23 months of age; doctor -diagnosed wheeze and persistent recurrent troublesome breathing; without obvious structural defect, suspicion of ciliary dyskinesia, cystic fibrosis, immune deficiency or specified use of corticosteroids. Airway hyperresponsiveness (AHR) was evaluated by performing a methacholine bronchial challenge test combined with whole body plethysmography and rapid thoracoabdominal compression. Endobronchial biopsies were analysed for remodeling (thickness of reticular basement membrane and amount of airway smooth muscle) and for inflammation (numbers of inflammatory cells). Correlation analyses were performed. RESULTS: Forty-nine infants fulfilled the inclusion criteria for the present study. Median age was 1.06 years (IQR 0.6; 1.5). Lung function was impaired in 39/49 (80%) children, at the median age of 1.1 years. Methacholine challenge was successfully performed in 38/49 children. Impaired baseline lung function was correlated with AHR (P = .047, Spearman). In children with the most sensitive quartile of AHR, the percentage of median bronchial airway smooth muscle % and the number of bronchial mast cells in airway smooth muscle were not significantly higher compared to others (P = .057 and 0.056, respectively). No association was found between AHR and thickness of reticular basement membrane or inflammatory cells. Only a small group of children with both atopy and AHR (the most reactive quartile) had thicker airway smooth muscle area than non-atopics with AHR (P = .031). CONCLUSIONS AND CLINICAL RELEVANCE: These findings do not support the concept that AHR in very young children with wheeze is determined by eosinophilic inflammation or clear-cut remodeling although it is associated with impaired baseline lung function. The possible association of increased airway smooth muscle area among atopic children with AHR remains to be confirmed.

Young children with moderate-to-severe atopic dermatitis can be treated safely and effectively with either topical tacrolimus or mild corticosteroids.

AIM: We collected evidence and safety data for topical tacrolimus in small children with atopic dermatitis (AD) and compared the usage with topical corticosteroid. METHODS: This was an interim analysis of 75 patients (55% female) at 1 year of an ongoing 3-year randomised open-label comparative follow-up study of topical tacrolimus vs corticosteroid treatment. One- to three-year-old children with moderate-to-severe eczema referred to the Skin and Allergy Hospital in Helsinki, Finland, were enrolled. RESULTS: Efficacy parameters, the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), transepidermal water loss (TEWL), eczema area, serum total immunoglobulin E (IgE) and the blood eosinophil count, showed improvement in both groups during the study. However, patients with signs of early sensitisation at baseline (elevated serum total IgE, elevated eosinophil count, positive prick tests or specific IgEs to aero or food allergens) had statistically significantly lower TEWL at the eczema site and a smaller eczema area at 12 months in the tacrolimus group. No severe adverse effects were seen during the treatment. CONCLUSION: Children with AD and signs of early sensitisation appeared to benefit more from early tacrolimus than corticosteroid treatment. Small children may need stronger but nevertheless safe ointment options when treating moderate-to-severe AD.

High-Dose Vitamin D Supplementation Does Not Prevent Allergic Sensitization of Infants.

OBJECTIVE: To investigate the effect of vitamin D supplementation dose on allergic sensitization and allergic diseases in infants, and to evaluate whether vitamin D status in pregnancy and at birth are associated with infant allergy outcomes. STUDY DESIGN: Altogether, 975 infants participated in a randomized, controlled trial of daily vitamin D supplementation of 10 µg (400 IU) or 30 µg (1200 IU) from the age of 2 weeks. At 12 months of age, food and aeroallergen IgE antibodies were measured, and the occurrence of allergic diseases and wheezing were evaluated. RESULTS: We found no differences between the vitamin D supplementation groups in food (OR, 0.98; 95% CI, 0.66-1.46) or aeroallergen sensitization at 12 months (OR, 0.76; 95% CI,0.34-1.71). Allergic diseases or wheezing did not differ between groups, except for milk allergy which occurred more often in infants administered 30 µg vitamin D compared with the 10 µg dose (OR, 2.23; 95% CI, 1.00-4.96). Infants with high cord blood 25-hydroxyvitamin D (≥100 nmol/L) had a higher risk of food allergen sensitization compared with those with lower 25(OH)D concentration (75-99.9 nmol/L; OR, 2.00; 95% CI, 1.19-3.39). CONCLUSIONS: High-dose vitamin D supplementation did not prevent allergic sensitization, allergic diseases, or wheezing during the first year of life. In contrast, we observed an increased risk of milk allergy in infants randomized to higher vitamin D supplementation, and an increased risk of allergic sensitization in infants with high cord blood vitamin D status, indicating a possible adverse effect of high concentrations of vitamin D.

Serum chitinase-like protein YKL-40 is linked to small airway function in children with asthmatic symptoms.

BACKGROUND: Lung function impairment among asthmatic children begins in early life, and biomarkers for identifying this impairment are needed. The chitinase-like protein YKL-40 has been associated with asthma and lung function in adults, but studies in children have yielded conflicting results. We evaluated the potential of YKL-40 and other systemic biomarkers for identifying lung function deficits in children with asthmatic symptoms. METHODS: We determined the levels of serum YKL-40, periostin, and high-sensitivity C-reactive protein (hs-CRP) from the blood samples of 49 children with asthmatic symptoms. Lung function was assessed with impulse oscillometry (IOS) and spirometry, combined with an exercise challenge and a bronchodilator test. Fractional exhaled nitric oxide was measured at multiple flow rates. RESULTS: Serum levels of YKL-40 showed significant correlations with most IOS indices at baseline (P = .008-.039), but there was no association between YKL-40 and spirometry parameters. Neither periostin nor hs-CRP were associated with baseline lung function. Children with a significant response in either the exercise challenge or the bronchodilator test had increased serum levels of YKL-40 (P = .003) and periostin (P = .035). YKL-40 correlated significantly with the blood neutrophil count (rs  = .397, P = .005) but was not associated with biomarkers of eosinophilic inflammation. CONCLUSION: Serum YKL-40 is a potential biomarker for lung function deficits in children with asthmatic symptoms. These deficits appear to be focused on small airways and may remain undetected with spirometry.

Outcome of oral immunotherapy for persistent cow's milk allergy from 11 years of experience in Finland.

BACKGROUND: The safety and efficacy of long-term milk oral immunotherapy (OIT) in Finnish children with persistent cow's milk allergy (CMA) were evaluated in an open-label, non-randomized study. METHODS: During the 11-year study, 296 children aged 5 years or older with immunoglobulin E (IgE)-mediated CMA started milk OIT. Follow-up data were collected at three time points: the post-buildup phase, 1 year thereafter, and at the cross-sectional long-term follow-up between January 2016 and December 2017. Patients were divided according to baseline milk-specific IgE (sIgE) level and by the amount of milk consumption at the long-term follow-up. The high-dose group consumed ≥2 dL of milk daily, while the failure group consumed <2 dL of milk or were on a milk-avoidance diet. RESULTS: Out of the initial study group, 244/296 (83%) patients participated in the long-term follow-up. Among these patients, 136/244 (56%) consumed ≥2 dL of milk daily. The median follow-up time was 6.5 years. Of the recorded markers and clinical factors, the baseline milk sIgE level was most associated with maintaining milk OIT (P < 0.001). Respiratory symptoms in the post-buildup phase increased the risk of treatment failure (OR 3.5, 95% CI: 1.5-8.1, P = 0.003) and anaphylaxis (OR 14.3, 95% CI: 1.8-114, P = 0.01). CONCLUSION: More than half of the patients were able to maintain the targeted milk dose in their daily diet. Baseline milk sIgE level and reactivity during the early treatment stage strongly predicted the long-term outcome and safety of milk OIT.

Airway hyperresponsiveness in young children with respiratory symptoms: A five-year follow-up.

BACKGROUND: Recurrent wheezing in early life is transient in most children. The significance of airway hyperresponsiveness (AHR) in persistence of respiratory symptoms from infancy to early childhood is controversial. OBJECTIVE: We evaluated whether AHR in wheezy infants predicts doctor-diagnosed asthma (DDA) or AHR at the age of 6 years. METHODS: Sixty-one wheezy infants (age 6-24 months) were followed up to the median age of 6 years. Lung function and AHR with methacholine challenge test were assessed at infancy and 6 years. The exercise challenge test was performed at the age of 6 years. Atopy was assessed with skin prick tests. RESULTS: At 6 years, 21 (34%) of the children had DDA. Children with DDA had higher logarithmic transformed dose-response slope (LOGDRS) to methacholine in infancy than children without DDA (0.047 vs 0.025; P = .033). Furthermore, AHR to methacholine in infancy and at 6 years were associated with each other (r = 0.324, P = .011). Children with exercise-induced bronchoconstriction (EIB) at 6 years were more reactive to methacholine in infancy than those without EIB (P = .019). CONCLUSION: Increased AHR in symptomatic infants was associated with increased AHR, DDA, and EIB at median the age of 6 years, suggesting early establishment of AHR.

Small airway function in children with mild to moderate asthmatic symptoms.

BACKGROUND: Clinical significance of small airway obstruction in mild pediatric asthma is unclear. OBJECTIVE: To evaluate small airway properties in children with mild to moderate asthmatic symptoms and the association of small airway function with asthma control and exercise-induced bronchoconstriction (EIB). METHODS: Children (5-10 years old) with recurrent wheezing (n = 42) or persistent troublesome cough (n = 16) and healthy controls (n = 19) performed impulse oscillometry (IOS), spirometry, and a multiple-breath nitrogen washout (MBNW) test. Exhaled nitric oxide (NO) was measured at multiple flow rates to determine alveolar NO concentration (Calv). Asthma control was evaluated with the Childhood Asthma Control Test (C-ACT), short-acting ß2-agonist (SABA) use within the past month, and asthma exacerbations within the past year. RESULTS: IOS, spirometry, and exhaled NO indexes that are related to small airway function differed between children with recurrent wheezing and healthy controls, whereas only forced expiratory flow at 25% to 75% of the forced vital capacity was associated with persistent cough. The MBNW indexes showed no difference between the groups. Among symptomatic children, conducting airway ventilation inhomogeneity and Calv were associated with asthma exacerbations (P = .03 and P = .002, respectively), and lung clearance index and Calv were associated with EIB (P = .04 and P = .004, respectively). None of the proposed small airway indexes was associated with the C-ACT score or SABA use. CONCLUSION: Subtle changes were observed in the proposed small airway indexes of IOS, spirometry, and exhaled NO among children with mild to moderate recurrent wheezing. Small airway dysfunction, expressed as ventilation inhomogeneity indexes and Calv, was also associated with asthma exacerbations and EIB.

Abnormal lung function at preschool age asthma in adolescence?

BACKGROUND: Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate. OBJECTIVE: This longitudinal study relates lung function assessed with impulse oscillometry (IOS) in preschool children to asthma in adolescence. METHODS: Lung function was measured with IOS in 255 children with asthma-like symptoms aged 4-7 years. Baseline measurements were followed by exercise challenge and bronchodilation tests. At age 12-16 years, 121 children participated in the follow-up visit, when lung function was assessed with spirometry, followed by a bronchodilation test. Asthma symptoms and medication were recorded by a questionnaire and atopy defined by skin prick tests. RESULTS: Abnormal baseline values in preschool IOS were significantly associated with low lung function, the need for asthma medication, and asthma symptoms in adolescence. Preschool abnormal R5 at baseline (z-score ≥1.645 SD) showed 9.2 odds ratio (95%CI 2.7;31.7) for abnormal FEV1/FVC, use of asthma medication in adolescence, and 9.9 odds ratio (95%CI 2.9;34.4) for asthma symptoms. Positive exercise challenge and modified asthma-predictive index at preschool age predicted asthma symptoms and the need for asthma medication, but not abnormal lung function at teenage. CONCLUSION: Abnormal preschool IOS is associated with asthma and poor lung function in adolescence and might be utilised for identification of asthma persistence.

Wheat oral immunotherapy was moderately successful but was associated with very frequent adverse events in children aged 6-18 years.

AIM: This study investigated oral immunotherapy (OIT) for children aged 6-18 years with wheat allergies. METHODS: Well-cooked wheat spaghetti was given to 100 children with wheat allergies every day for 17 weeks, increasing from 0.3 to 2000 mg of wheat protein, followed by three- and nine-month maintenance phases. Blood samples were taken before therapy and at follow-up visits. The study was carried out in 2009-2015 in four Finnish paediatric allergology units. RESULTS: The children (67% male) had a mean age of 11.6 years (range 6.1-18.6), and 57 were using wheat daily 16 months after the initiation of therapy. Allergic symptoms occurred in 94/100 children: mild in 34, moderate in 36 and severe in 24. Specific immunoglobulin E (IgE) for ω-5-gliadin was significantly higher in patients who did not reach the target dose and were related to the intensity of reactions. CONCLUSION: The majority (57%) of children with wheat allergies could use wheat in their daily diet 16 months after the initiation of OIT, but 94/100 had adverse reactions and 60 were moderate or severe. Specific IgE to ω-5-gliadin may provide a biomarker for how much wheat can be tolerated and the intensity of the reactions to immunotherapy.

Measurement of tidal breathing flows in infants using impedance pneumography.

Tidal breathing flow volume (TBFV) profiles have been used to characterise altered lung function. Impedance pneumography (IP) is a novel option for assessing TBFV curves noninvasively. The aim of this study was to extend the application of IP for infants and to estimate the agreement between IP and direct pneumotachograph (PNT) measurements in assessing tidal airflow and flow-derived indices.Tidal flow profiles were recorded for 1 min simultaneously with PNT and uncalibrated IP at baseline in 44 symptomatic infants, and after methacholine-induced bronchoconstriction in a subgroup (n=20).The agreement expressed as the mean deviation from linearity ranged between 3.9 and 4.3% of tidal peak inspiratory flow, but was associated with specific airway conductance (p=0.002) and maximal flow at functional residual capacity (V'maxFRC) (p=0.004) at baseline. Acute bronchoconstriction induced by methacholine did not significantly affect the agreement of IP with PNT. TBFV indices derived from IP were slightly underestimated compared to PNT, but were equally well repeatable and associated with baseline V'maxFRC (p=0.012 and p=0.013, respectively).TBFV profiles were consistent between IP and PNT in most infants, but the agreement was affected by reduced lung function. TBFV parameters were not interchangeable between IP and PNT, but had a similar association with lung function in infants.

Vitamin D, high-sensitivity C-reactive protein, and airway hyperresponsiveness in infants with recurrent respiratory symptoms.

BACKGROUND: Vitamin D insufficiency might be associated with biased T-cell responses resulting in inflammatory conditions such as atopy and asthma. Little is known about the role of vitamin D in low-grade systemic inflammation and airway hyperresponsiveness (AHR) in young children. OBJECTIVE: To evaluate whether vitamin D insufficiency and increased serum high-sensitivity C-reactive protein (hs-CRP) are linked to AHR in symptomatic infants. METHODS: Seventy-nine infants with recurrent or persistent lower respiratory tract symptoms underwent comprehensive lung function testing and a bronchial methacholine challenge test. In addition, skin prick tests were performed and serum 25-hydroxyvitamin D (S-25-OHD), hs-CRP, total immunoglobulin E, and blood eosinophil levels were determined. RESULTS: S-25-OHD was lowest in infants with blood eosinophilia and AHR (n = 10) compared with those with eosinophilia only (n = 6) or AHR only (n = 50) or those with neither (n = 13; P = .035). Moreover, vitamin D insufficiency (S-25-OHD <50 nmol/L) was most common in infants with blood eosinophilia and AHR (P = .041). Serum hs-CRP was lower in infants with recurrent physician-diagnosed wheezing (P = .048) and in those with blood eosinophilia (P = .015) than in infants without these characteristics and was not associated with S-25-OHD or AHR. S-25-OHD levels were significantly lower (median 54 nmol/L) during the autumn-winter season than in the spring-summer season (median 63 nmol/L; P = .026). CONCLUSION: Vitamin D insufficiency could underlie eosinophilia and AHR in infants with troublesome lung symptoms, whereas hs-CRP-mediated low-grade systemic inflammation is rare in early childhood wheezing.

Tidal flow variability measured by impedance pneumography relates to childhood asthma risk.

Lung function variability is a fundamental feature of asthma but has been difficult to quantify in children due to methodological limitations. We assessed the feasibility and clinical implications of overnight flow variability measurement at home using impedance pneumography in young children.44 children aged 3-7 years with recurrent or persistent lower airway symptoms were recruited. Patients were divided into high- or lower-risk groups (HR and LR groups) based on their risk of asthma (modified Asthma Predictive Index), and a third group was formed of children who had a history of wheeze and who were treated with inhaled corticosteroids (ICS group). Tidal volume and the derived flow were recorded through skin electrodes using impedance pneumography at home during sleep. Quantities describing overnight change in expiratory flow-volume minimum curve shape correlation (CSRmin) and respiratory chaoticity (minimum noise limit (NLmin)) were derived.Recordings were successful in 34 children. CSRmin differed between the HR and LR groups (p=0.002) and between the HR and ICS groups (p=0.003), indicating a stronger change in flow profile shape in the HR group. NLmin differed between the HR and LR groups (p=0.014), indicating momentarily lowered chaoticity in the HR group.Impedance pneumography was found feasible for quantifying nocturnal lung function variability and the measured variability was associated with risk of asthma in young children.